The ALS Clinical Research Center established with funding from the NINCDS will substantiate and extend our initial discoveries related to the cause and mechanisms of amyotrophic lateral sclerosis (ALS). These will be correlated with concurrent serial studies of the various cooperating sections together with continuous neurological characterization of the clinical status and stages of patients. Autoimmune humoral and cell-mediated immune mechanisms or specifically enhanced cell-mediated immunity will be quantitated with certain antigens (polio or related picornovirus, adeno-associated virus (AAV) and neoantigens present in ALS CNS fractions isolated by the neurochemistry section). Initial studies showing immune complexes in ALS blood, central nervous system (CNS) and kidney will be extended for identification and specificity of the antibodies and identification of the antigen present in immune complexes. Virology studies will continue initial findings of AAV and possible other virus in ALS CNS, and will use special probes for presence of polio and related virus and AAV in CNS and extra-CNS tissues, including pseudotype evidence of latent viral infection. Pathological mechanisms including changes of neurofibrillar axon ballooning and tubulin abnormalities, possibly systemic, will be explored. Neurochemical studies will extend the initial changes of abnormal ganglioside distribution in frontal lobe of ALS-CNS to motor areas of brain and spinal cord. The confirmation by the nerve culture program of a motor neuron cytotoxic factor in ALS sera as reported by others will be extended with characterization studies as the factor and future intracerebral transfer of neurocytotoxic factor on a continuous basis to properly prepared animals. Biostatistical analysis of these interrelated findings should give insight for investigative work on specific clinical management of ALS.